Prognostic value of Ki-67 for prostate cancer death in a conservatively managed cohort

Abstract

Background: Standard clinical parameters cannot accurately differentiate indolent from aggressive prostate cancer. Our previous work showed that immunohistochemical (IHC) Ki-67 improved prediction of prostate cancer death in a cohort of conservatively treated clinically localised prostate cancers diagnosed by transurethral resection of the prostate (TURP). Here, we present results in a more clinically relevant needle biopsy cohort.

Methods: Biopsy specimens were microarrayed. The percentage of Ki-67 positively stained malignant cells per core was measured and the maximum score per individual used in analysis of time to death from prostate cancer using a Cox proportional hazards model.

Results: In univariate analysis (n=293), the hazard ratio (HR) (95% confidence intervals) for dichotomous Ki-67 (≤ 10%, >10%) was 3.42 (1.76, 6.62) χ(2) (1 df)=9.8, P=0.002. In multivariate analysis, Ki-67 added significant predictive information to that provided by Gleason score and prostate-specific antigen (HR=2.78 (1.42, 5.46), χ(2) (1 df)=7.0, P=0.008).

Conclusion: The IHC Ki-67 scoring on prostate needle biopsies is practicable and yielded significant prognostic information. It was less informative than in the previous TURP cohort where tumour samples were larger and more comprehensive, but in more contemporary cohorts with larger numbers of biopsies per patient, Ki-67 may prove a more powerful biomarker.

Figure 1

Hazard ratio for Ki-67 in multivariate analysis after adjustment for covariates, in the existing literature, for (A) prostate cancer-specific survival (I-squared=7.5%, P=0.371) and (B) prostate cancer recurrence (I-squared=61.9%, P=0.007). The area of the box is proportional to the amount of information available, and the horizontal bars represent 95% confidence intervals.

Figure 2

Consort diagram: overview of cohort.

Figure 3

Distribution of Ki-67 score, in diagnostic needle biopsy tissue from a conservatively managed cohort of 293 men.

Figure 4

Kaplan–Meier estimates of prostate cancer death according to Ki-67 score in three groups: different categories of Ki-67 score are shown by different lines: solid, ⩽5% dotted, >5 to ⩽10% dashed, >10%.

Figure 5

Hazard ratio for prostate cancer mortality for Ki-67 score (⩽10%, >10%) within different clinical subgroups of Gleason score and prostate-specific antigen (PSA). The area of the box is proportional to the amount of information available and the horizontal bars represent 95% confidence intervals. The lowest Gleason group (<7) and PSA group (⩽4 ng ml⁻¹) were omitted because there was only one observation in each of these groups.